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Nitric oxide and endothelial cell aging

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Abstract

Nitric oxide (NO) is a crucial factor for the integrity and function of the endothelium. Besides its role in blood pressure regulation, NO acts antithrombotically and antiapoptotically. The laminar flow in the blood vessel, called shear stress, is the most potent endogenous protective force against endothelial cell apoptosis, mostly by increasing the expression of the endothelial NO synthase (eNOS) and thereby increasing NO bioavailability in endothelial cells. However, during the process of endothelial cell aging, shear stress is unable to induce eNOS expression and protect against apoptosis induction. Moreover, apoptosis induction is correlated with aging in vivo, suggesting a link between NO bioavailability, aging, and apoptosis. Moreover, cellular aging is accompanied with an increase in reactive oxygen species (ROS), which results in an imbalance of the redox status of the cell. Thioredoxin is an important redox regulator in endothelial cells and can “bind” NO. S-nitrosylation of thioredoxin increases its enzymatic activity, which in turn leads to reduced intracellular ROS and apoptosis, suggesting that thioredoxin may play an important role in NO bioavailability. One crucial step in the process of cellular aging is the telomerase activity that is reduced in aged endothelial cells. NO can inhibit the decrease in telomerase activity and thereby delay the onset of replicative senescence. Thus, the reduction in NO bioavailability is a crucial factor for endothelial cell aging and apoptosis.

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We apologize for the failure to cite many of the important and relevant papers in this field.

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Correspondence to Judith Haendeler.

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Haendeler, J. Nitric oxide and endothelial cell aging. Eur J Clin Pharmacol 62 (Suppl 1), 137–140 (2006). https://doi.org/10.1007/s00228-005-0008-8

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